Organ transplantation is the therapy of choice for endstage organ failure. In the case of kidney failure, for example, transplantation provides for increased life expectancy, enhanced quality of life, and is more cost-effective than maintaining patients on hemodialysis. In the case of extrarenal organs, transplantation is life-saving since no equivalent to hemodialysis exists for these organs.
Rejection of the transplanted graft is an immunological response in which the recipient's immune system recognizes the graft as “foreign” and attempts to eliminate the transplanted graft. Part of the response involves binding of the recipient's antibodies to the donor's vascular endothelial cells lining the blood vessels within the transplanted graft. Antibody deposition leads to the activation of the complement cascade which mediates a cytotoxic phenomenon which can directly damage or kill the endothelial cells.
In addition the complement cascade leads to the activation of the endothelial cells which causes subsequent change in the anticoagulant environment. More specifically, the vascular endothelium normally provides a nonthrombogenic surface; however, when activated by the immune system during the rejection process, the endothelial lining transforms into a procoagulant environment. The resultant prothrombotic (thrombogenic) surfaces then attract polymorphonuclear cells and platelets, resulting in the endothelium being damaged and causing separation from the underlying substratum, and ultimately, severe thrombosis of the graft.
The standard approach to mitigating the rejection process is to treat the transplant recipient daily with an immunosuppressive regimen. However, currently immunosuppressive regimens are systemic; i.e., in addition to suppressing immune function against the transplanted graft, immune function which protects the recipient from other processes (such as infections) is suppressed. Further, the currently available immunosuppressants may cause substantial non-specific, toxic effects on cell types other than cells of the immune system.
U.S. Pat. No. 5,643,712 describes a method for treating and rendering grafts nonthrombogenic and substantially nonimmunogenic using an extracellular matrix coating. Disclosed is a material that can be applied to the luminal surface of the blood vessels of a vascularized tissue or organ.